Acral lentiginous melanoma: histopathological prognostic features of 121 cases

BACKGROUND: Acral lentiginous melanoma (ALM) is the fourth histopathological subtype of malignant melanoma, accounting for < 10% of all melanomas in white-skinned populations. It is characterized by a lentiginous pattern of proliferation of the intraepidermal component of the tumour. Its individualization is still controversial, especially in regard of its prognostic value. OBJECTIVES: To characterize better ALM from a pathological point of view and to assess the prognostic value of all histopathological features of ALM. METHODS: We performed a review of all cases of ALM followed from 1996 to 2004 at the University Hospital Department of Dermatology, Lyon, France. We examined all haematoxylin, eosin and saffron-stained tissue sections of the primary lesions. Several pathological parameters of interest in melanoma were evaluated for disease-free and specific survival with the Kaplan-Meier method and the Cox proportional hazards regression model. RESULTS: Representative histological material was available for 121 patients. The mean Breslow thickness was 2.5 mm (in situ-20 mm). Fifteen lesions (12%) were in situ, nine (7%) were at Clark level II, 35 (29%) at III, 40 (33%) IV and 22 (18%) V. Extension along adnexal structures was found in almost half of the ALMs (46%), without prognostic significance. Seventeen (14%) lesions showed no microscopic pigmentation. Remnants of pre-existing naevus were found in four (3%) melanomas. The width of the 36 (30%) ulcerated lesions ranged from 1 to 20 mm (mean 7.6). Ulceration and its width were both associated with a large tumour thickness (P < 0.01), a high level of invasion (P < 0.01), the presence of vascular invasion (P < 0.01) and the lack of pigment production (P < 0.01). Among the 99 ALMs which were in the vertical growth phase (VGP), 21 showed a high mitotic rate (> 6 mitoses mm(-2)). A high mitotic rate was found to be significantly associated with the presence of ulceration (P < 0.01). The presence of microscopic satellites was noted in 10 (10%) lesions. The uncommon presence of small cells (8%) in the VGP was statistically significantly (P < 0.01) associated with a worse prognosis compared with other cell types. Multivariate analysis identified mitotic rate (P < 0.01), microsatellites (P = 0.05), Clark level (P = 0.01) and gender (P = 0.03) as independent prognostic factors for disease-free survival. Only the presence of microsatellites (P = 0.02) and a high mitotic rate (P < 0.01) were independently correlated with specific survival in ALM. CONCLUSIONS: This is a detailed pathological study of a large cohort with ALM, an uncommon subtype of melanoma. Mitotic activity appears to be of particular importance in predicting the outcome of ALM.